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Hantavirus : 

Hantavirus 1 @vishal

Virus classification : 

Virus classification Group: Group V ((-)ssRNA) Order: Unassigned Family: Bunyaviridae Genus: Hantavirus Type species: Hantaan virus 2 @vishal

Species: : 

Species: 1.Andes virus2.Amur virus3.Azagny virus4.Bayou virus5.Black Creek Canal virus6.Cano Delgadito virus7.Calabazo virus8.Carrizal virus9.Catacamas virus10.Choclo virus11.Dobrava-Belgrade virus12.El Moro Canyon virus13.Hantaan virus14.Huitzilac virus 3 @ vishal

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15.Imjin virus16.Isla Vista virus17.Khabarovsk virus18.Laguna Negra virus19.Limestone Canyon virus20.Monongahela virus21.Montano virus22.Mouyassue virus23.Muleshoe virus24.Muju virus25.New York virus26.Nova virus27.Oran virus28.Playa de Oro virus 4 @vishal

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29.Prospect Hill virus30.Puumala virus31.Rio Mamore virus 32.Rio Segundo virus33.Sangassou virus34.Saaremaa virus35.Seoul virus36.Sin Nombre virus37.Soochong virus38.Tanganya39.Thailand virus40.Thottapalayam virus41.Topografov virus42.Tula virus 5 @vishal

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Humans may be infected with hantaviruses through rodent bites, urine, saliva or contact with rodent waste products. Some hantaviruses cause potentially fatal diseases in humans, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Human infections of hantaviruses have almost entirely been linked to human contact with rodent excrement, but recent human-to-human transmission has been reported with the Andes virus in South America. 6 @vishal

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The name hantavirus is derived from the Hantan River area in South Korea. Member of the group: Hantaan virus (HTNV), isolated in the late 1970s by Ho-Wang Lee and colleagues. HTNV is one of several hantaviruses that cause HFRS, formerly known as Korean hemorrhagic fever. 7 @vishal

History: : 

History: The hantaviruses are a relatively newly discovered genus of viruses. Several thousand United Nations soldiers became ill with "Korean haemorrhagic fever" (now called HFRS) during the Korean War. This outbreak sparked a 25-year search for the etiologic agent. It has been proposed that the mysterious sweating sickness was a caused by a previously unknown hantavirus, therefore making the first appearance before the Battle of Bosworth Field. 8 @vishal

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In 1993, an outbreak of Hantavirus pulmonary syndrome (HPS) occurred in the south-western United States. The viral cause of the disease was found later and was called the Sin Nombre virus (SNV, in Spanish, "Virus sin nombre", for "nameless virus"). Its rodent host, Peromyscus maniculatus (deer mouse), was first identified by Terry Yates, a professor at the University of New Mexico. In addition to Hantaan virus and Sin Nombre virus, several other hantaviruses have been implicated as etiologic agents for either HFRS or HPS. 9 @vishal

Genome: : 

Genome: Hantaviruses are enveloped viruses with a genome that consists of three single-stranded, negative sense RNA segments designated S (small), M (medium), and L (large). The S RNA encodes the nucleocapsid (N) protein. The M RNA encodes a polyprotein that is cotranslationally cleaved to yield the envelope glycoproteins Gn (formerly G1) and Gc (formerly G2). The L RNA encodes the L protein, which functions as the viral transcriptase/replicase. 10 @vishal

Virions: : 

Virions: Hantavirus virions are about 100 nanometres (nm) in diameter. Enveloped by glycoproteins, known as G1 and G2, are encoded by the M segment of the viral genome. 11 @vishal

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These are composed of many copies of the nucleocapsid protein N, which interact with the three segments of the viral genome to form helical structures. The density of the virions is 1.18 gram per cubic centimeter. These features are common to all members of the Bunyaviridae. @vishal 12

Life cycle : 

Life cycle Entry into host cells is thought to occur by attachment of virions to cellular receptors and subsequent endocytosis. Nucleocapsids are introduced into the cytoplasm by pH-dependent fusion of the virion with the endosomal membrane. Subsequent to release of the nucleocapsids into cytoplasm, the complexes are targeted to the ER-Golgi Intermediate compartments (ERGIC) through microtubular associated movement resulting in the formation of viral factories at ERGIC. These factories then facilitate transcription and subsequent translation of the viral proteins. 13 @vishal

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Transcription of viral genes must be initiated by association of the L protein with the three nucleocapsid species. In addition to transcriptase and replicase functions, the viral L protein is also thought to have an endonuclease activity that cleaves cellular messenger RNAs (mRNAs) for the production of capped primers used to initiate transcription of viral mRNAs. As a result of this "cap snatching," the mRNAs of hantaviruses are capped and contain nontemplated 5' terminal extensions. 14 @vishal

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The G1 (aka Gn) and G2 (Gc) glycoproteins form hetero-oligomers and are then transported from the endoplasmic reticulum to the Golgi complex, where glycosylation is completed. The L protein produces nascent genomes by replication via a positive-sense RNA intermediate. Hantavirus virions are believed to assemble by association of nucleocapsids with glycoproteins embedded in the membranes of the Golgi, followed by budding into the Golgi cisternae. Nascent virions are then transported in secretory vesicles to the plasma membrane and released by exocytosis. 15 @vishal

Pathogenesis : 

Pathogenesis The pathogenesis of Hantavirus infections is unclear as there is a lack of animal models to describe it (rats and mice do not seem to acquire severe disease). While the primary site of viral replication in the body is not known, In HFRS, there is increased vascular permeability and decreased blood pressure due to endothelial dysfunction and the most dramatic damage is seen in the kidneys, whereas in HPS, the lungs, spleen, and gall bladder are most affected. 16 @vishal

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Early symptoms of HPS tend to present similarly to the flu (muscle aches, fever and fatigue) and usually show up around 2 to 3 weeks after exposure. Later stages of the disease (about 4 to 10 days after symptoms start) will include difficulty breathing, shortness of breath and coughing. @vishal 17

Transmission: : 

Transmission: @vishal 18

Prevalence : 

Prevalence Regions especially affected by HFRS include China, the Korean Peninsula, Russia and northern and westernEurope. 19 @vishal

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Regions with the highest incidences of HCPS include Argentina, Chile, Brazil, United States, Canada and Panama. The agent of HCPS in South America: Andes virus(also called Oran, Castelo de Sonhos, Lechiguanas, Juquitiba, Araraquara, and Bermejo viruses and many other synonyms), which is the only hantavirus that has shown uncommonly an interpersonal form of transmission. In the U.S., minor cases of HCPS include New York virus, Bayou virus, and possibly Black Creek Canal virus. @vishal 20

Symptoms : 

Symptoms Hemorrhagic fever with renal syndrome: Hantavirus has an incubation time of two to four weeks in humans before symptoms of infection occur. The symptoms of HFRS can be split into five phases: 1. Febrile phase: Symptoms include fever, chills, sweaty palms, diarrhea, malaise, headaches, nausea, abdominal and back pain, respiratory problems such as the ones common in the influenza virus, as well as gastro-intestinal problems. These symptoms normally occur for three to seven days and arise about two to three weeks after exposure. 21 @vishal

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2. Hypotensive phase: This occurs when the blood platelet levels drop and symptoms can lead to tachycardia and hypoxemia. This phase can last for 2 days. 3. Oliguric phase: This phase lasts for three to seven days and is characterised by the onset of renal failure and proteinuria occurs. 4. Diuretic phase: This is characterized by diuresis of three to six litres per day, which can last for a couple of days up to weeks. 5. Convalescent phase: This is normally when recovery occurs and symptoms begin to improve. Formerly known as Korean hemorrhagic fever, HFRS is the term accepted by the World Health Organization. 22 @vishal

Hantavirus (cardio-)pulmonary syndrome : 

Hantavirus (cardio-)pulmonary syndrome Hantavirus pulmonary syndrome (HPS) is an often fatal disease caused by hantavirus infection. The symptoms are very similar to those of HFRS and include tachycardia and tachypnea. Additionally, patients will develop difficulty breathing, coughing and shortness of breath. Such conditions can lead to a cardiopulmonary phase, where cardiovascular shock can occur, and hospitalization of the patient is required. 23 @vishal

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HPS was first recognized in 1993 in the southwest of the United States by Bruce Tempest MD, and was originally called "Four Corners disease". It has since been identified throughout the United States. Although rare, HPS is fatal in up to 60% of cases. Rodent control in and around the home remains the primary strategy for preventing hantavirus infection. People suspecting illness are encouraged to contact their local health department. @vishal 25

Weaponization : 

Weaponization Korean hemorrhagic fever (Hantavirus) was one of three hemorrhagic fevers and one of more than a dozen agents that the United States researched as potential biological weapons before suspending its biological weapons program. 26 @vishal

Prevention and treatment : 

Prevention and treatment There is no known antiviral treatment, but natural recovery from the virus is possible. Patients with suspected hantavirus are usually admitted to hospital and given oxygen to help them breathe.  As the virus can be transmitted by rodent saliva, excretia and bites, control of rats and mice in areas frequented by humans is key for disease prevention. General prevention can be accomplished by disposing of rodent nests, sealing any cracks and holes in homes where mice or rats could get in, laying down poisons or using natural predators such as cats in the home. 27 @vishal

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Evolution: : 

Evolution: Findings of significant congruence between phylogenies of hantaviruses and phylogenies of their rodent reservoirs have led to the theory – well accepted until recently–of long-standing hantavirus–rodent host coevolution. Various hantaviruses have been found to infect multiple rodent species, and cases of cross-species transmission (host switching) have been recorded. Additionally, rates of substitution based on nucleotide sequence data reveal that hantavirus clades and rodent subfamilies may not have diverged at the same time. Furthermore, hantaviruses have been found in multiple species of shrews and moles. 29 @vishal

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Taking into account the inconsistencies in the theory of coevolution, Ramsden et al. in 2009 have proposed that the patterns seen in hantaviruses in relation to their reservoirs could be attributed to preferential host switching directed by geographical proximity and adaptation to specific host types. Ulrich et al. in 2010 have proposed that the observed geographical clustering of hantavirus sequences may have been caused by an isolation-by-distance mechanism. 30 @vishal

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Upon comparison of the hantaviruses found in hosts of orders Rodentia and Soricomorpha, Yanagihara et al. in 2011 have proposed that the evolutionary history of the hantavirus consists of a complex mix of both host switching and codivergence. It suggest that ancestral shrews or moles rather than rodents may have been the early original hosts of ancient hantaviruses. 31 @vishal

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1.Andes virus: Andes virus (ANDV) is a hantavirus, which, in South America, is a major causative agent of Hantavirus Cardiopulmonary Syndrome (HCPS or HPS). ANDV causes lethal disease in the Syrian Hamster that closely models the course of disease progression in humans, including a rapid progression from first symptoms to death, including fluid in the pleural cavity and the histopathology of the lungs and spleen. The availability of this model allows for the study of various drugs and other treatments that may have an impact on the treatment of all HCPS-causing hantavirus infections 32 @vishal

2.Playa de Oro virus: : 

2.Playa de Oro virus: Playa de Oro virus (OROV) is a probable species of hantavirus found in the rodents Oryzomys couesi and Sigmodon mascotensis in the Mexican state of Colima. The former is thought to be the main host. The sequences of parts of the virus's RNA-based genome have been determined; they differ by 7–10% in amino acid composition and 22–24% in nucleotide composition from closely related viruses. It is currently treated as a probable species in the Hantavirus genus. 33 @vishal

3.Puumala virus: : 

3.Puumala virus: Puumala virus is a species of hantavirus. Humans infected with the virus may develop a haemorrhagic fever with renal syndrome (HFRS) known as ’nephropathia epidemica’. Puumala virus HFRS is lethal in a small percentage of cases. It has been theorized that Puumala virus, unlike other members of the genus Hantavirus, may also have lethal effects on its rodent host. Puumala virus was discovered and named in 1980 by researchers in Finland. 34 @vishal

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Puumala virus is named after a municipality in Finland. The virus is found predominantly in Scandinavia and Finland, although it has also been reported elsewhere in Northern Europe, Poland and Russia. The bank vole (Myodes glareolus) acts as a reservoir for the virus, nephropathia epidemica cases track with the vole population in a three- to four-year cycle. Humans are infected through inhalation of dust from vole droppings. @vishal 35

4.Seoul virus: : 

4.Seoul virus: Seoul virus is a species of hantavirus. It can cause a form of hemorrhagic fever. 36 @vishal

5.Virus sin Nombre: : 

5.Virus sin Nombre: The Sin Nombre virus (roughly translated as "the nameless virus" in Spanish) (SNV) is the prototypical etiologic agent of hantavirus cardiopulmonary syndrome (HCPS). Its original name was "Four Corners virus" or "Navajo Flu", but the name was changed after local residents raised objections. 37 @vishal

History : 

History It was first isolated from rodents collected near the home of one of the initial patients with hantavirus pulmonary syndrome (HPS) in the Four Corners region of the western United States. Isolation was achieved through blind passage in Peromyscus maniculatus (deer mouse) and subsequent adaptation to growth in Vero E6 cells. 38 @vishal

Epidemiology : 

Epidemiology SNV occurs wherever its reservoir rodent carrier, (the deer mouse Peromyscus maniculatus) is found, which includes essentially the entire United States except for the far southeastern region. SNV can be contracted through the inhalation of virus-contaminated deer mouse excreta. The case fatality ratio of SNV-induced HCPS in the USA was reported to be about 66.7% (CDC, 1993). However, since that time the case fatality ratio has steadily declined as more mild cases came to be recognized. By 2007 the CFR had declined to about 35%. 39 @vishal

Diagnosis: : 

Diagnosis: The nested RT-PCR assay developed during the initial HCPS outbreak provided a rapid method for the genetic characterization of novel hantaviruses that did not require a virus isolate. Numerous new hantaviruses have been detected by RT-PCR in rodent tissues but have yet to be associated with human disease. These include El Moro Canyon virus associated with the western harvest mouse Reithrodontomys megalotis. @vishal 40

The folllowing tests may be done: : 

The folllowing tests may be done: Blood tests to check for signs of hantavirus Complete blood count (CBC) Complete metabolic panel Kidney and liver function tests X-ray of the chest @vishal 41

Thank you : 

Thank you 42 @vishal

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